The present invention is directed to a technique and apparatus for obtaining morphological and biochemical information from a sample site. More particularly, the present invention is an optical probe, system and technique of sequentially or concurrently acquiring morphological and biochemical information from a sample site to more quickly, reliably and efficiently analyze and characterize the status (e.g., pathological, morphological, biochemical, and physiological state) of the suspicious tissue (e.g., a lesion, tumor, or plaque) within the site.
Current methods for screening and diagnosis of pathologic conditions in tissue such as cancer often involve surgical biopsy of the tissue followed by histological evaluation. This procedure is not only invasive, time-consuming and expensive but often is not capable of rapid and reliable screening of a large surface such as that of the oral cavity. Since early diagnosis and treatment tend to be critical to effective and successful treatment of these pathologies, the development of better techniques and devices for diagnosis and screening would result in improved clinical outcomes.
Non-invasive optical methods, such as fluorescence spectroscopy, for the detection of certain biochemical changes associated with early neoplastic development have been described. These techniques are particularly sensitive to malignant tissue transformation. However, such techniques are limited in wide spread adoption because they are unable to provide information with regard to the morphology of the tissue and, as such, often result in a xe2x80x9cfalse positives.xe2x80x9d
Optical coherence tomography (OCT) is a non-invasive imaging modality which allows high resolution of tissue microstructure imaging with resolution on the order of microns. This technique measures detailed changes within a few millimeters of a non-transparent tissue structure. The currently the primary shortcoming of the OCT imaging modality is the time required to obtain images over a sufficient area.
Boppart et al., xe2x80x9cForward Imaging Instruments for Optical Coherence Tomographyxe2x80x9d Optics Letters, Vol.22(21): 1618-1620 (1997) describes a technique and device which employs endoscopic and OCT imaging modalities. In this regard, Boppart et al. employs a conventional endoscope having a white light illumination source, in a conventional manner, to visually inspect the target tissue. Boppart et al., after detecting suspicious tissue (for example, on a suspicious polyp or bump or discolored spot) within the target, employs an OCT imaging device to further study the suspicious tissue. Boppart et al., however, directs the OCT probe onto that tissue using the white light (light which is visible to the human) image.
Importantly, Boppart does not employ a xe2x80x9cfluorescence imagexe2x80x9d to guide the OCT probe to the suspicious tissue within the target. Fluorescence imaging is a sensitive optical modality for detecting the presence of suspicious tissues (for example, cancers and other biochemical processes) before the appearance of any visual cuesxe2x80x94that is cues which are visible to the human eye via white light. In addition, fluorescence photons may originate from points below the surface of the target thereby enhancing the likelihood of identifying suspicious tissue well before the appearance of any visual evidence of, for example, cancer.
The present invention improves on the Boppart et al. technique and device by incorporating a means for obtaining biochemical information directly through spectroscopic imaging or sensing. In this regard, the present invention employs a fluoroscopic, near infrared (NIR) absorption spectroscopic, NIR reflectance spectroscopic, Raman spectroscopic, and/or magnetic resonance spectroscopic approach to detect suspicious tissue within a target sample and, upon detecting the suspicious tissue, employs OCT to study the morphology of the tissue in detail. Thus, the present invention combines OCT with a technique and means for obtaining spectroscopic information as well as visual information concurrently or sequentially from the same site. The present invention may be employed, for example, whenever spectroscopic and morphological information are desired or necessary. The techniques and devices of the present invention may be applied in the medical field including such applications as: (1) cancer detection and differentiation of benign lesions from pre-malignant and malignant lesions as well as staging of superficial tumors; (2) detection and classification of atherosclerotic plaques; (3) monitoring tissue changes; (4) intraoperative means for assessing tissue removal and for administration of drugs; (5) monitoring pharmacokinetic drug distribution as a function of morphology; (6) intraoral examination of dental tissues (hard and soft); and (7) monitoring changes in tissue (e.g., the cervix) architecture and bio-composition following treatments or during pregnancy.
It should be noted that the techniques and devices of the present invention may also be employed in such situations where simultaneous OCT imaging and optical spectroscopic information are desirable, such as materials characterization, plant physiology, and industrial process monitoring.
Thus, there is a need for a technique and apparatus to investigate and image the morphological and biochemical properties in the first few millimeters of a biological structure with a high degree of spatial resolution to facilitate the analysis of the pathological, morphological and physiological state of the structure. There is a need for a method and device to provide regional biochemical information followed by a closer more detailed inspection of the tissue structure. The invention described herein provides a highly sensitive, specific, and rapid means of non-invasive identification of potentially cancerous lesions based on spectroscopic measurement as well as a means for more detailed morphologic characterization using OCT to image the tissue architecture and spectroscopy to image the biochemical content or status of the tissue.
In a first aspect, the present invention is an optical imaging probe to provide information representative of morphological and biochemical properties of a sample (e.g., cancerous tissue). The optical imaging probe may include a spectroscopic imaging probe element, an OCT imaging probe element, an optical probe window, and a reflective optical filter. The reflective optical filter may be disposed within an optical path between the optical window and the spectroscopic and OCT imaging probe elements and positioned to receive radiation incident on the optical probe window and to provide radiation of a first wavelength to the spectroscopic imaging probe element and to provide radiation of a second wavelength to the OCT imaging probe element. The optical probe of this aspect of the invention facilitates sequential or concomitant OCT imaging and spectroscopic (e.g., fluoroscopic) imaging.
Moreover, the OCT information and the spectroscopic information is obtained sequentially or concomitantly without movement of the OCT/spectroscopic probe relative to the sample under investigation. That is, morphologic and biochemical related information is obtained of the sample without movement of the OCT/spectroscopic probe. This facilitates accurate registration between the OCT image and the spectroscopic image. Thus, a relatively large area (e.g., the oral cavity) may be rapidly and non-invasively scanned for biochemical anomalies and morphological characteristics of those anomalies with precise registration.
In a second principle aspect, the present invention is an imaging system which includes a spectroscopic imaging system, an OCT imaging system, a data analysis unit, and an OCT/spectroscopic imaging probe. In this aspect, the OCT/spectroscopic imaging probe includes a spectroscopic imaging probe element to facilitate imaging using a spectroscopy imaging technique, an OCT imaging probe element to facilitate an OCT imaging technique, and a reflective optical filter. The reflective optical filter is disposed within an optical path between an optical window of the OCT/spectroscopic imaging probe and the spectroscopic and OCT imaging probe elements. In addition, the reflective optical filter is positioned to receive radiation incident on the optical probe window and to provide radiation of a first wavelength to the spectroscopic imaging probe element and to provide radiation of a second wavelength to the OCT imaging probe element so that the OCT/spectroscopic imaging probe allows sequential or concomitant OCT imaging and spectroscopic imaging.
In a preferred embodiment, the spectroscopic imaging system and the OCT system are electrically, optically and/or physically coupled to the data analysis unit. The data analysis unit receives the biochemical and morphological information and allows an operator or physician to analyze that information to assess the pathological, morphological and physiological state of the structure. In this regard, the data analysis unit allows the operator or physician to quickly, reliably and efficiently analyze and characterize the status (e.g., pathological, morphological, biochemical, and physiological state) of the suspicious tissue (e.g., a lesion, tumor, or plaque). This analysis and characterization may be done in real time or off-line.
The spectroscopic imaging system may be fluoroscopic, NIR absorption spectroscopic, NIR reflectance spectroscopic, Raman spectroscopic, magnetic resonance spectroscopic and/or infrared based (i.e., sensing spatial temperature using).